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Sorafenib response in hepatocellular carcinoma: MicroRNAs as tuning forks
Shruthi Kanthaje1, Ankita Makol1, Anuradha Chakraborti1
1Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Abstract:
Hepatocellular carcinoma (HCC) is the primary liver malignancy that contributes towards the second most common cause of cancer-related mortality. The targeted chemotherapeutic agent, sorafenib, is known to show a statistically significant but limited overall survival advantage in advanced HCC. However, the individual patient response towards sorafenib varies drastically, with most experiencing stable disease and few with partial response; complete response is very rare. Progressive disease despite the treatment is also evident in many patients, indicating drug resistance. These varied responses have been linked with the modulation of several intracellular signaling pathways. Notably, the regulation of these pathways through diverse operating biomolecules, including microRNAs (miRNAs), is the focus of recent studies. MicroRNAs are tiny, non-coding RNA molecules that regulate the expression of several target genes. In addition, miRNAs are known to play a role in the progression of HCC carcinogenesis. Interestingly, miRNAs have also been identified to play differential roles in terms of sorafenib response in HCC such as biomarkers and functional modulation of cellular response to sorafenib, hence, they are also being therapeutically evaluated. This review outlines the role of reported miRNAs in different aspects of sorafenib response in HCC.
Insights
MicroRNAs (miRNAs) influence hepatocellular carcinoma (HCC) treatment responses to sorafenib. This review explores how these small RNA molecules act as biomarkers and functional modulators in HCC patients receiving sorafenib therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide.
- Sorafenib is a targeted therapy for advanced HCC, offering limited survival benefits.
- Patient responses to sorafenib vary significantly, with many developing drug resistance.
Purpose of the Study:
- To review the role of microRNAs (miRNAs) in hepatocellular carcinoma (HCC) progression.
- To explore the involvement of miRNAs in modulating cellular responses to sorafenib.
- To highlight miRNAs as potential biomarkers and therapeutic targets for sorafenib resistance in HCC.
Main Methods:
- Literature review of studies investigating microRNAs in HCC.
- Analysis of research on miRNA regulation of intracellular signaling pathways relevant to sorafenib.
- Examination of studies evaluating miRNAs as biomarkers for sorafenib response and resistance.
Main Results:
- MicroRNAs (miRNAs) are implicated in the carcinogenesis and progression of HCC.
- Specific miRNAs demonstrate differential roles in influencing patient response to sorafenib.
- miRNAs can act as biomarkers for predicting sorafenib efficacy and resistance in HCC.
Conclusions:
- MicroRNAs play a critical role in the variable responses observed in hepatocellular carcinoma patients treated with sorafenib.
- Targeting miRNAs offers a promising strategy for overcoming sorafenib resistance and improving therapeutic outcomes in HCC.
- Further research into miRNA-based diagnostics and therapeutics is warranted for advanced HCC management.
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